Cunnane · Nature reviews. Drug discovery 2020 · narrative review · n=?

Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.

Cited 1021 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanisms and therapeutic concepts without systematic search or meta-analysis.

PubMed 32709961 · doi:10.1038/s41573-020-0072-x · record verified 2026-08-29

What was done

This narrative review synthesized the mechanistic basis and prospective therapeutic strategies for countering brain energy deficits in age-related neurodegenerative disorders, with a primary focus on Alzheimer disease. It examined physiological pathways of cerebral ATP generation (oxidative phosphorylation, glycolysis, ketone utilization, and exercise-derived lactate) and outlined interventions designed to restore or compensate for progressive glucose hypometabolism.

What was found

The abstract reports no quantitative empirical data or statistical results. It outlines potential therapeutic modalities including restoring oxidative phosphorylation and glycolysis, augmenting insulin sensitivity, correcting mitochondrial dysfunction, administering ketone-based interventions, delivering energy-modulating hormones, applying RNA therapeutics, and implementing multimodal lifestyle changes.

Why it matters

It frames cerebral energetic deterioration as a targetable driver of neurodegeneration that begins presymptomatically, highlighting metabolic rescue as an alternative or complementary therapeutic strategy to traditional disease-modifying targets.

Limits

The abstract provides no original experimental or clinical trial data, quantitative metrics, or systematic synthesis of treatment efficacy. Details regarding specific patient populations, clinical stages, and comparative treatment safety are absent.

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